Electrical sensor systems are widely applied to the analyses and measurements of the analytes in biological samples, e.g. glucose concentration, cholesterol concentration, etc. in the blood. Generally, this kind of electrochemical measuring systems includes a test strip and a meter. In particular, the test strip is designed for single-time usage and is disposable for the convenience in home life.
So far several generations of the methods for analyzing and measuring the glucose concentration in a blood sample have been developed. However, general glucose concentration meters use glucose oxidase enzymes (GOD) and mediators. Typically, the mediator is potassium ferricyanide. In the test strip with the mediator, the mechanisms for the reactions among the glucose in a sample, the GOD and the mediator and the subsequent testing reactions are listed as follows.Glucose+GOD(ox)→Gluconic acid+GOD(red)  (1)GOD(red)+2M(ox)→2M(red)+GOD(ox)+2H+  (2)2M(red)(Apply Voltage)→2M(ox)+2e−  (3)
In the above chemical equations, M(ox) represents the mediator in an oxidation state and M(red) represents the mediator in a reduction state. The same representation way is adopted for the GOD. As shown in the above equations (1)-(3), the glucose is oxidized by the GOD(ox), the electron is transferred to the GOD(ox), and the GOD(ox) receives the electron and then is transformed into GOD(red). Next, the reduced GOD(red) transfers the electron to the M(ox), that is, the M(ox) is reduced into M(red), which is diffused to the surface of the electrode. Under the application of a fixed voltage, electronic signals are interchanged between the M(red) and the electrode, i.e. an electrochemical oxidation-reduction reaction. In such recirculation reactions, a sensed electrical current is generated and is proportional to the glucose concentration in the blood sample.
As the concentration of the analyte in the sample is measured by sensing the electrical current, the sensed electrical current is called Cottrell current according to the following equation:i(t)=K n F A C D0.5 t−0.5 
where i is an instant value of the sensed current;
K is a constant;
n is the transferred electron number (For example, n is equal to 2 in the equation (3));
F is the Faraday constant;
A is the surface area of the working electrode;
C is the concentration of the analyte in the sample;
D is the diffusion coefficient of the reagent;
t is a specific time period, during which a predetermined voltage is applied to the electrodes.
The concentration C of the analyte is to be determined. This concentration is proportional to the sensed current i. Because the sensed current is also proportional to the surface area A of the working electrode, a precisely determined surface area of the working electrode of the test strip is a key factor for accurate measurements.
In additions, as shown in the Cottrell Equation, the time-dependent sensed current decreases with the square root of the time period, during which the predetermined voltage is applied to the electrodes. Therefore, the time point when a voltage is applied to the electrodes for the control of the instant measurement of the Cottrell current is another important factor for accurate measurements.
Some examples of such sensors and meters are disclosed in the patents of U.S. Pat. No. 5,266,179, U.S. Pat. No. 5,366,609 or EP 1 272 833.
The operation methods for the meters disclosed in these patents are approximately the same. First, a test strip is inserted into a meter. A proper insertion of the test strip into the meter is detected by mechanical and/or electrical switches or contacts. Once a test strip is properly inserted into the meter, the user is requested to provide a sample, typically a drop of the user's blood. The blood sample then enters a reaction zone on the test strip. The reaction zone of the test strip has at least two electrodes, which are covered by the reagent.
A drawback of the conventional meter is related to the issue of detecting the presence of the sample. In a sample presence detection period, a voltage is applied to the electrodes to detect whether the sample exists in the reaction zone. However this voltage causes the consumption of the electrical current, i.e. the consumption of the electrons, and this electrical current is generated by the reaction between the reagent and the sample. The consumed electrical current is relevant to the concentration of the analyte in the sample. Thus, the consumed current in the sample presence detection period for checking the sample presence results in a deviation on the measurement. Specially, when the volume of the sample is small or the measuring time is short, the issue of the consumption of the electrical current becomes serious.
Once the sample with sufficient volume exists in the reaction zone, the sample and the reagent are mixed in a specific time period in a second step. This specific time period is called an incubation period. After the incubation is finished, the measurement proceeds in a third step in a time period called test period.
Another issue for the conventional meters is related to the incubation period. The incubation period is afforded to allow the mixing and dissolving between the sample and the reagent, and a specific time period is required to complete these mixing and dissolving. The complete dissolution is affected by some parameters, e.g. the room temperature and the condition of the blood sample. For example, the dissolving becomes slow, when the room temperature is low or the fat concentration in the blood sample is high. If the measurement proceeds before the dissolution is completed, the instable sensed current will be generated. Thus, the incubation period must be sufficient for the longest time of the dissolution to make sure that the accurate measurement can be attained in all conditions.
If a voltage is applied during the incubation period, the electrical current is consumed during the incubation period. Since the dissolution conditions are varied from time to time, the consumed quantity of the electrical current is not stable. Thus, the application of the voltage during the incubation period would result in some deviations on the measurement. On the other hand, if no voltage is applied during the incubation period, longer time is required to reach the complete mixing and dissolving between the sample and the reagent, and meanwhile the accuracy of the measurement may be influenced by the oxygen interference, though the consumption of the electrical current during the incubation period can be avoided.
In the conventional method for operating the voltages to measure the blood sugar in U.S. Pat. No. 4,224,125, when a sample enters into a measuring device, a predetermined voltage is applied to the electrodes, and then the relationship of the steady current and the concentration is measured without power-off. Although the method without power-off can effectively aid the dissolution between the sample and the reagent, meanwhile more electrical current is consumed. Thus, the reaction strength of the analyte cannot be accumulated, the signal strength is reduced, and then the deviations of the measurement occur.
Besides, it is disclosed in the U.S. patents of U.S. Pat. No. 5,108,564 and U.S. Pat. No. 5,352,351 that if no voltage is applied in an open circuit during the incubation period, though the consumption of the electrical current can be avoided, but the oxygen bubbles inside the sample are generated and aggregated on the surface of the electrodes, the effective working area of the electrode is reduced to affect the accuracy of the measurement, and longer time is required to reach the complete mixing and dissolving between the sample and the reagent. Another drawback of the conventional meters is related to the issue of the existence of the interference material in the electrochemical test strip. The interference material, e.g. uric acid, vitamin C (ascorbic acid), acetaminophen, other in vivo metabolic materials, or in vitro introduced materials, can affect the measurement results of the blood sugar or other analytes. The US patent with U.S. Pat. No. 5,653,863 discloses a method of the voltage application as: (1) when the sample enters the meter, the positive voltage, called burn-off pulse, is applied between the two electrodes for 1-15 seconds at the voltage of 0.1-0.9 volt to reduce the background deviation; (2) in a delay period for 10-40 seconds, it is instantly powered off in an open circuit state to interrupt the electrochemical oxidation-reduction reaction; (3) the read pulse is provided to measure the concentration of the analytes. When the sample enters the meter, the application of the burn-off voltage for a long time can reduce the background interference. However, the application of the burn-off voltage also causes more consumption of the electrical current. Although it is powered off in the incubation period to reduce the current consumption, longer time is required to reach the complete mixing and dissolving between the sample and the reagent, and meanwhile the oxygen interference may occur to result in the deviations of the measurement.
For solving the above drawbacks of the conventional techniques, the Taiwan patent with the patent No. 1334026 discloses an operation method for the meter, wherein series of pulses are applied to the electrodes of the test strip during both the sample detection period and incubation period so as to reduce the current consumption, to eliminate the generation of the oxygen bubbles, to effectively aid the mixing between the sample and the reagent, to shorten the mixing time and to raise the accuracy of the measurement. In this patent, the maximum value of the voltage applied during the incubation period is high enough to oxidize the mediator in the reagent on the test strip from a reduction state into an oxidation state, and low enough to avoid oxidizing the hydrogen peroxide, but is not high enough to oxidize the interference materials in the sample.
As known from the above mentioned conventional techniques, the accuracy for the relationship between the electrical current and the concentration of the analyte is not satisfied and needs to be raised. The present invention provides methods for operating the measurements to reduce the current consumption, to eliminate the oxygen interference, to sustain the steady and accurate working area of the electrodes and to largely enhance the accuracy of the measurement result. The present invention introduces the application of the voltage during an interference-removal period so that the measured current during the test period after the interference-removal period would not be affected by the interference materials in order to significantly raise the accuracy of the measurement and to overcome the issues occurring in the convention techniques, and the accurate measurement results for the analyte can be successfully obtained in spite of small volume of the sample and/or short measuring time.